Ligand-induced regulation of ERalpha and ERbeta is indicative of human breast cancer cell proliferation

Abstract

Two estrogen receptors (ER), ERalpha and ERbeta, are expressed in breast cancer but their role in treatment response is unclear. The overall objective of this study was to determine if the presence of ERbeta protein in breast cancer cell lines is an indicator of a poor prognosis based on cell proliferation. In addition, we determined the effect of estradiol (E2) and selective estrogen receptor modulators (SERMs), such as tamoxifen and genistein, on ERalpha and ERbeta protein regulation, to help in the understanding of the mechanism behind their role in modulating cell proliferation. Using western blot and immunofluorescence analysis, the ER positive cell lines, MCF-7 and T47D, were found to contain both ERalpha and ERbeta, and thus were used as model systems. E2 and genistein, which increased cell proliferation in both cell lines, induced an up regulation of ERbeta in both cell lines. This suggests that an estrogenic response in breast cancer cells is indicated by an increase in ERbeta expression. Tamoxifen decreased cell proliferation in both cell lines, while up regulating ERalpha in both cell lines, suggesting that antiestrogenic response is indicated by an increase in ERalpha expression. Although a change in the ERalpha/ERbeta ratio may play a role in the effect seen in cell proliferation, this study indicates that ERbeta is a poor prognosticator of cell proliferation in breast cancer and that ERalpha is a positive prognosticator of responsiveness to antiestrogen treatment.